• formulation;
  • physical stability;
  • solid dispersion;
  • thermodynamics;
  • thermal analysis


Important consideration for developing physically stable solid dispersion is miscibility of drug in carrier matrix. It is possible to predict thermodynamics of binary system through free energy calculations based on Flory–Huggins interaction parameter (χdp). In present study, PEG 6000 as model polymer and dataset comprising commonly used drugs/excipients was selected. The three-dimensional solubility parameter based on group contribution method was utilized for systemic calculation of χdp of the polymer with each compound in data set. On the basis of the values of χdp, it was possible to categorize all the compounds into three distinct categories, Types I and II: compounds predicted to be miscible and immiscible respectively with the polymer in all proportions and Type III: compounds expected to exhibit composition dependent miscibility behavior. The Bagley plot showed that majority of points for Type I fall in a region, which can approximately be delimited by a circle. Experimental verification through thermal analysis revealed that though it was possible to predict correctly miscibility behavior of Type II class compounds, distinction between Types I and III was less evident. Hence, solubility parameter based χdp may be used as an initial tool for fast screening of immiscible combination of polymer and drug. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2254–2263, 2013